Pharmacokinetic/Pharmacodynamic Modeling of Seven Antimicrobials for Empiric Treatment of Adult Bloodstream Infections with Gram-Negative Bacteria in China.

Abstract

Objective: Optimal dosing regimens for achieving a positive clinical outcome were simulated for seven antibiotics commonly used to treat bloodstream infections (BSIs) in adults. Methods and Results: Pharmacokinetic/pharmacodynamic (PK/PD) modeling was used to simulate 17 regimens, including meropenem, imipenem, cefepime, ceftazidime, piperacillin-tazobactam, tigecycline, and polymyxin B based on patients' characteristics and the antimicrobial resistance data for the main pathogens isolated from blood specimens in Shandong province (China). A regimen for which the cumulative fraction of response (CFR) was 90% or more was considered optimal. For Escherichia coli and Klebsiella pneumoniae, all carbapenem regimens, ceftazidime (2gq8h, 0.5 hr, and 3hr infusion), and piperacillin/tazobactam (4.5gq8h, 3 hr infusion) achieved CFRs above 90%. The meropenem regimen (2gq8h, 3 hr) achieved CFRs above 90% for both ceftriaxone or cefotaxime-resistant (CRO/CTX-R) E. coli and K. pneumoniae. For Pseudomonas aeruginosa, ceftazidime and meropenem (2gq8h, 0.5 hr, and 3 hr infusion) achieved optimal CFRs. None of the β-lactam regimens examined achieved a CFR above 80% for Acinetobacter baumannii. For all examined bacteria, polymyxin B (50 mg q12h) led to a CFR above 90%. Conclusion: PK/PD modeling based on local antimicrobial resistance data provides valuable guidance for clinicians for the administration of empirical antibiotic treatments for BSIs.